J. Am. Chem. SOC.1993,115,8835-8836
Zirconium-Mediated,Highly Diastereoselective Ring Contraction of Carbohydrate Derivatives: Synthesis of Highly Functionalized, Enantiomerically Pure Carbocycles
8835
Scheme I
Scheme II Hisanaka Ito, Yoshiteru Motoki, Takeo Taguchi,’ and Yuji Hanzawa Tokyo College of Pharmacy 1432- I Horinouchi, Hachioji Tokyo 192-03, Japan
1
Received March 22, I993 Ring contraction of carbohydrate derivatives is one of the significant methods for constructing functional, enantiomerically pure carbocycles,1,2which have considerable utility in the synthesis of biologically active c o m p o ~ n d s . ~In recent contributions, intramolecular radical c y c l i ~ a t i o n l bor ~ ~metal-mediated ~~ intramolecular coupling reactions5of carbohydrate derivatives are noteworthy. Recently, generation and reactions of zirconacycles, which could be easily prepared by treating a zirconocene equivalent (“Cp2Zr”) with unsaturated compounds, have been extensively developed.6 During the course of our studies of the “CpZZr” chemistries,’ we have reported a method for preparing allylic zirconiums by treating allyl ethers with “Cp2Zr” (Scheme I). To extend the possibility of our allylic zirconium chemistry, we examined the intramolecular cyclizations of allylic zirconium reagents. We report herein the novel “Cp2Zr”-mediated, highly stereoselective ring contraction of vinyl carbohydrate derivatives and a reaction mechanism based on an N M R study of the reactive allylic zirconium intermediate. In the initial work with the 6-vinyl cyclic acetal derivatives 1, the ring contraction proceeded smoothly to give cis-2-vinylcyclopentanol(2) as a single isomer ( 8 7 % ~ i e l dunder ) ~ the conditions of “Cp2Zr” and BF3-OEt2 in THF (Scheme II).9 This procedure was applicable to vinyl carbohydrate derivatives (3,5,7,10,11, (1) Recent reports on ring contraction of cyclic ethers to carbocycles: (a) Verner, E. J.; Cohen, T. J . Am. Chem. SOC.1992,114,375-377. (b) Vite, G. D.; Alonso, R. A.; Fraser-Reid, B. J. Org. Chem. 1989,54,2268-2271. (c) Alonso, R. A.; Vite, G. D.; McDevitt, R. E.; Fraser-Reid, B. J . Org. Chem.
1992,57, 573-584. (2)For reviews of carbohydrate as a chiral synthon, see: (a) Inch, T. D. Tetrahedron 1984,40, 3161-3213. (b) Hanessian, S. Total Synthesis of Natural Products: The Chiron Approach; Pergamon Press: Oxford, 1983. (c) Fraser-Reid, B.; Anderson, R. Prog. Chem. Org. Nut. Prod. 1980,39, 1-61. (3) For reviews, see: (a) Ogawa, S. J. Synth. Org. Chem. Jpn. 1985,43, 26-39. (b) Borthwick, A. D.; Biggadike, K. Tetrahedron 1992,48,571-623. (c) Huryn, D. M.; Okabe, M. Chem. Rev. 1992,92,1745-1768. See also: (d) Trost, B. M.; Li, L.; Guile, S.D. J . Am. Chem. SOC. 1992,114,8745-8747. ( e )Trost, B. M.; Van Vranken, D. L. J . Am. Chem. SOC. 1993,115,444-458, and references cited therein. (4)(a) Wilcox, C.S.; Thomasco, L. M. J . Org. Chem. 1985,50,546-547. (b) Tsang, R.; Fraser-Reid, B. J. Am. Chem. SOC.1986,108,2116-2117.(c) Wilcox, C. S.;Gaudino, J. J. J . Am. Chem. SOC. 1986,108,3102-3104.(d) RajanBabu, T. V. J . Am. Chem. SOC. 1987,109,609-611.( e ) Nugent, W. A,; RajanBabu, T. V. J. Am. Chem. SOC. 1988, 110, 8561-8562. (f) RajanBabu, T. V. J. Org. Chem. 1988,53,4522-4530. (8) RajanBabu, T. V.; Fukunaga, T.; Reddy, G. S.J. Am. Chem. SOC. 1989,Ill, 1759-1769. (5) (a) Enholm, E. J.; Satici, H.; Trivellas, A. J . Org. Chem. 1989,54, 1989,111, 5841-5843. (b) Enholm, E. J.; Trivellas, A. J . Am. Chem. SOC. 64636465. (c) RajanBabu, T. V.; Nugent, W. A.; Taber, D. F.; Fagan, P. J. J. Am. Chem. SOC. 1988,110,7128-7135. (6)(a) Negishi, E.; Cederbaum, F. K.; Takahashi, T. Tetrahedron Lett 1986,27, 2829-2832. See also: (b) Swanson, D. R.; Negishi, E. Organometallics 1991,10,825-826.For reviews on zirconacycles, see: (c) Negishi, E. Chem. Scr. 1989,29,457-468.(d) Buchwald, S. L.; Fisher, R. A. Chem. Scr. 1989,29,417-421.(e) Buchwald,S. L.;Nielsen,R. B. Chem. Rev. 1988, 88, 1047-1058. (f) Negishi, E.; Takahashi, T. Synthesis 1988,1-19. (7)(a) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992,33, 1295-1298. (b) Ito, H.;Nakamura,T.;Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992,33,3769-3772.(c) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992,33,4469-4472.(d) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33,7873-7876. (e) Ito, H.; Taguchi, T.; Hanzawa, Y. J. Org. Chem. 1993,58,774-775.
2 87% cis only
13, and 16),1° and the results are shown in Table 1 , I I 5-Vinylpyranoside 3, which is easily prepared from methyl OL-Dglucopyranoside, was converted to carbocycle 4 in toluene by sequential treatment with “Cp2Zr” and BF3.OEtt in 65% yield as a single isomer (entry 1). In the absence of BFs.OEt2, uncyclized aldehyde 18was obtained (80%)after acidic hydrolysis, along with a trace amount of 4. This fact suggests the presence of a stable intermediate which is converted to 4 or 18upon addition of BF3.OEt2 or 1 N HC1 (vide infra). Similar treatment of 5 with “CpzZr” in THF followed by addition of BFs-OEtz gave carbocycle 6 in excellent diastereoselectivity in 75% yield (entry 2). The stereochemistry of the product was unaffected by the absence or presence of BFyOEt2. Our strategy was also applicable to the synthesis of highly functionalized cyclobutane derivatives. In the reaction of methyl D-glucofuranoside derivatives 10 and 11, both anomeric isomers gave cyclobutane derivative 12 in low yields without any difference in reactivity (entries 4 and 5).12 Replacement of the 3-alkoxy1 group of 10 by a hydrogen atom, 3-deoxyfuranoside (13), or a benzyloxymethyl substituent, 3-deoxy-3-(benzyloxymethyl)furanoside(la), improved the yield of products (14,15,and 17) significantly (60% and 77%, entries 6 and 7) under the influence of BF3.OEt2. In all cases examined, complete cis-selectivity between the hydroxyl and vinyl groups is noteworthy. The stereochemical relationships between the new chiral centers and inherent carbohydrate substituents in the products were heavily dependent on the stereochemistry of the 4- or 3-substituent of the starting pyranoside or furanoside, respectively, rather than the stereo(8) The cis-stereochemistry of 2 was confirmed by comparing the NMR spectrum with that of the reported trans-isomer, see: (a) Hegedus, L. S.; McKearin, J. M. J . Am. Chem. SOC. 1982,104,2444-2451. (b) Yadav, V.; Fallis, A. G. Can. J. Chem. 1991, 69,779-789. (9)Typical experimental procedure: to a solution of CpZr(nBu)z, prepared in situ by the reaction of zirconocenedichloride (246mg, 0.84mmol) in THF or toluene (4 mL) with 2 equiv of n-butyllithium in hexane at -78 OC for 1 h, was added a solution of starting vinyl carbohydrate (0.7mmol) in THF or toluene (3 mL) at -78 OC, and the temperature was raised to ambient temperature. After being stirred for 3 h, a solution of BF,.OEt2 (1.4mmol) in THF or toluene (2mL) was added at 0 “C, and stirring was continued for 2 h at ambient temperature. Next, 1 N HC1 was added and extracted with dichloromethane. The combined organic layers were washed with brine, dried over MgSOd, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. (10) Preparative procedures of starting carbohydrate derivatives (3,s.7, 10,11,13,and 16). 3 and 7 were prepared from methyl a-D-glucopyranoside and methyl a-D-mannopyranoside, respectively, according to an analogous method reported for 5. Tatsuta, K.; Niwata, Y.; Umezawa, K.; Toshima, K.; Nakata, M.J . Antibiot. 1991,44,456-458. 10 and 11 were prepared from 1,2:5,6-di-O-isopropylidene-a-~-glucofuranose. Sherk, A. E.; Fraser-Reid, B. J . Org. Chem. 1982,47,932-935.13was prepared according to theabovementioned procedure from 3-deoxy-1,2:5,6-di-O-isopropylidene-a-~-ribohexofuranoside. Iacono, S.;Rasmussen, J. R. Org. Synth. Collect. Vol. VII 1990, 139-141. 16 was prepared as in the case of 10 and 11 from 3-C(benzyloxymethyl)-3,5,6-trideoxy1,2-~isopropylidene-a-D-rib~5-bexenofuranose. Nakata, M.;Enari, H.; Kinoshita, M. Bull. Chem. SOC. Jpn. 1982,
55, 3283-3296. (1 1) All products are new compounds, and the structures were determined by IH and 13C NMR, phase-sensitive NOESY, HRMS, and combustion analysis. Full details are described in supplementary material. (12)The reaction was carried out without using BF3.OEt2. The addition of BFs.OEt2, as in the case of pyranoside derivatives, gave a complex reaction mixture, and the yield of the desired product was much lower.
OOO2-7863/93/ 1515-8835$04.OO/O 0 1993 American Chemical Society
8836 J. Am. Chem. SOC.,Vol. 115, No. 19, 1993 Table I. entry
Communications to the Editor
"CmZr"-Mediated Ring Contraction Reaction yield (%)"
substratelo
..
4
20 A
20 B Figure 1. Diastereofacial differentiation of the allylic zirconium double bond in the oxocarbenium transition state.
Scheme III r
\
BnqO ?)E 3n OMe
BnO 6Bn 11
I
pen.\ OH
I
1
BnOp"OBn 12
woMe { ,
19 (36Ib
*OH
1-"OBn 4
1 3 bBn
&m .N .
OH
60 14:15~3:1
15 u'OOBn
7
woMe ,
BnO -*
'oBn
16
776
BnO -8'1 "bBn
~
(I
NOE correlation
o x = 13; I
Numbers in parentheses are yields in the absence of Lewis acid.
* >98% de. Minor isomer could not be detected with 300-MHz IHNMR.
chemistry of the 2-substituent of the starting compound (entries 3 and 6). The stereochemistry of the vinyl group in all of the products was trans to the adjacent benzyloxy or benzyloxymethyl group. It deserves comment that the diastereoselectivity between the new chiral centers and the benzyloxy group in the reaction of 13is conspicuously low compared to other reactions (entry 6). The origin of the complete stereoselectivity in the present ring contractions was investigated by obtaining clean N M R spectral data of the intermediate 19derived from 3 and "CpzZr" in toluene without adding BF3-OEt2 (vide ante) as shown in Scheme III.I3 Significant features of the N M R spectrum of 19 were the olefin (13) 'H NMR (400 MHz, benzene-d6): 6 7.71-7.07 (m, 15 H, aromatic), 6.51 (dt, J = 8.0, 10.3 Hz, 1 H, 4-H), 5.94 (s, 5 H, Cp), 5.62 (s, 5 H, Cp), 5.11 (s, 1 H, 9-H), 5.10 ( d , J = 11.5 Hz, 1 H, benzylic), 5.04 ( d , J = 11.5 Hz, 1 H, benzylic), 5.03 (t, J = 10.3 Hz, 1 H, 5-H), 4.85 (d, J = 11.5 Hz, 1 H, benzylic), 4.82 (d, J = 11.5 Hz, 1 H, benzylic), 4.71 (d, J = 11.5 Hz, 1 H, benzylic), 4.66 (d, J = 11.5 Hz, 1 H, benzylic), 4.50 (m, 1 H, 6-H), 3.84-3.79 (m, 2 H, 7- and 8-H), 2.98 (s, 3 H, OMe), 2.74 (t. J = 10.3 Hz, 1 H, 3-H'), 0.98 (dd, J = 8.0, 10.3 Hz, 1 H, 3-H). "C NMR (100.6 MHz, benzene-ds): 6 141.2, 140.6, 139.8, 139.6, 129.2-127.1 (aromatic), 115.2, 110.8, 110.5, 103.2, 82.7, 81.1, 75.3, 75.1, 74.2,68.0, 54.6, 42.4.
OBn 18
protons at 6.51 and 5.03 ppm with a cis coupling constant (10.3 Hz)I4 and the absence of an aldehyde proton. The cis relationship of olefinic portion was further confirmed by the significant N O E correlations between the olefinic protons and also between the allylic protons (Scheme 111). The proof of 19 as an intermediate in the reaction of 3 (entry 1) was confirmed by the xnversion of 19to 4 upon addition of BF3.OEt2. It is probable thai BFrOEt2 accelerates the elimination of the methoxyl group through coordination to the methoxy oxygen of 19 to form oxocarbenium ion 20A or 20B. The stereoselectivity of the present reaction can be explained by comparing the pseudochair transition-state models ofZOAandZOB(Figure 1). It isobviousthatthestericallyfavored transition state is 20A. Therefore, it is reasonable that the low diastereoselectivity of the deoxy derivative 13 is a result of the inability of the substituent at the 3-position of the furanoside to control the stereochemistry of the product. The easy access to a variety of vinyl carbohydrate derivatives should make this approach a viable method for the preparation of enantiomerically pure and highly functionalized carbocycles. In conclusion, we opened a new avenue for an efficient and stereoselective construction of highly functionalized carbocycles by applying "Cp2Zr" chemistry to carbohydrate derivatives. The present procedure provides an alternative method to the reported proced~rel-~ for the preparation of highly functionalized optically pure carbocycles. Acknowledgment. We thank Professor H. Shindo and Mrs. C. Sakuma at Tokyo College of Pharmacy for helpful discussion on the N M R experiments. Supplementary Material Available: 'H, 13CN M R spectra and listing of specific rotation, IR, HRMS, elemental analysis, and N O E data of products 4, 6,8, 9, 12, 14, 15, and 17 (20 pages). Ordering information is given on any current masthead page. (14) The olefinic coupling constants 1 4 1 6 and 12 Hz for the (E)- and (2)-allylic zirconium derivatives, respectively, have been reported. See: Mashima, K.; Asami, K.; Yasuda, H.; Nakamura, A. Chem. Lett. 1983,219222.
